Kinetic and dynamic interaction of brotizolam and ethanol.

Abstract

Thirteen healthy male volunteers ingested a single 0.25 mg dose of the thienodiazepine hypnotic, brotizolam, on two occasions: once with a typical social cocktail (containing 60 ml of vodka), and in a second trial with an 'ethanol-placebo' cocktail. Brotizolam kinetics were determined from multiple plasma concentrations measured during the 24 h after dosage. Coadministration of brotizolam with ethanol, as opposed to the placebo cocktail, slightly imparied brotizolam clearance (1.85 vs 2.19 ml min-1 kg-1 P less than 0.005), increased peak plasma concentrations (5.3 vs 4.3 ng ml-1, P less than 0.05), and prolonged elimination half-life (5.2 vs 4.4 h, P less than 0.05). There was evidence of impairment of performance, although not statistically significant, for the first 4-6 h after brotizolam dosage in the reaction time test, the digit-symbol substitution test, and a tracking task. None of these was enhanced by ethanol. In both trials, brotizolam produced significant increases in self-rated perceptions of sedation, fatigue, feeling 'spaced-out', and thinking slowed down. These effects were more intense during the brotizolam-ethanol as compared to brotizolam-placebo. In both trials, recovery was essentially complete by 6-8 h after dosage. Coadministration of brotizolam with ethanol produces a small but significant impairment of brotizolam clearance. Brotizolam produced self-rated perceptions of sedation and fatigue during 4-6 h after dosage, but objective impairment of psychomotor performance was minimal. Subjective perceptions of sedation were enhanced by ethanol coadministration, but the effects on psychomotor performance were not.

• Authors: J M Scavone, D J Greenblatt, J S Harmatz, R I Shader
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 21 Issue 2 Pg. 197-204 (Feb 1986) ISSN: 0306-5251 [Print] England
• PMID: 3954936 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Azepines
• Hypnotics and Sedatives
• Ethanol
• brotizolam

Topics

• Adult
• Azepines (metabolism, pharmacology)
• Chromatography, Gas
• Drug Interactions
• Ethanol (metabolism, pharmacology)
• Humans
• Hypnotics and Sedatives (metabolism, pharmacology)
• Kinetics
• Male
• Psychomotor Performance (drug effects)
• Reaction Time (drug effects)
• Thinking (drug effects)